Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42–58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3–5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8–12; 60.9%, 48.8% and 24.6% between weeks 20–24; and 59.7%, 48.3% and 24.6% between weeks 44–48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469–0.817) and patient’s age (OR: 1.016; 95%CI: 1.005–1.026) were associated with 50% response at weeks 20–24. The variables that were associated with a higher reduction of headache days between weeks 20–24 were patient’s age (0.068; 95% CI: 0.018–0.119) and headache days per month at baseline (0.451; 95% CI: 0.319–0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626—0.538) and daily headache at baseline (-2.718; 95% CI: -4.58—0.869) were associated with fewer reduction in the number of headache days between weeks 20–24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-023-01690-2.